P721: VALIDATION OF THE MOLECULAR INTERNATIONAL PROGNOSTIC SCORING SYSTEM IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES DEFINED BY INTERNATIONAL CONSENSUS CLASSIFICATION
Authors: Wan Hsuan Lee, Ming-Daw Tsai, Chien-Chin Lin, Cheng-Hong Tsai, Feng-Ming Tien, Min-Yen Lo, Mei-Hsuan Tseng, Yuan-Yeh Kuo, Ming-Chih Liu, Jih-Luh Tang, Hsun -I Sun, Yi-Kuang Chuang, Wen-Chien Chou, Hsin-An Hou, Hwei-Fang Tien
Journal: HemaSphere (2023)

Background: Myelodysplastic syndrome (MDS) is a heterogeneous clonal myeloid neoplasm with varied prognoses. A risk-adapted treatment strategy is mandatory to optimize treatments in patients with MDS. Recently, under the aegis of the International Working Group for Prognosis in MDS, a molecular prognostic model (International Prognostic Scoring System-Molecular [IPSS-M]) has been proposed. In addition, the 2022 International Consensus Classification (ICC) recategorized myeloid neoplasms emphasizing the integration of clinical, molecular, and pathologic parameters and introduced new entities and refined criteria of existing diagnostic categories. Aims: In the present study, we aimed to validate the IPSS-M based on an Asian MDS cohort defined by 2022 ICC and identify patients who may benefit from novel risk stratification model from a therapeutic standpoint. We compared the prognostic power of the IPSS-M with IPSS and IPSS-R. The impacts of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in different risk categories of the IPSS-M were also evaluated. Methods: According to 2022 ICC, a total of 649 patients with primary MDS who had adequate cryopreserved bone marrow samples for deep-targeted sequencing at diagnosis were recruited. We applied the web calculator (https://mds-risk-model.com/) to calculate the IPSS-M scores. TruSight myeloid sequencing panel (Illumina) and the HiSeq platform were adopted to analyze the gene alterations of 54 myeloid-neoplasm relevant genes. Analysis of FLT3-ITD was performed via PCR, followed by fluorescence capillary electrophoresis and that of KMT2A-PTD, by PCR followed by Sanger sequencing because of the limitation of NGS in detecting these two mutations. Five genes (ETNK1, GNB1, NF1, PPM1D, and PRPF8) from the residual group of 15 genes defined by the IPSS-M model were not included. Results: According to the IPSS-M, 62.2% of patients had moderate high (14.2%), high (18.6%) or very high-risk (29.4%) disease, while 18 (2.8%), 132 (20.3%), and 95 (14.6%) patients were at very low, low, or moderate low-risk respectively. The strong poor prognostic predictors including TP53 mutation, FLT3 mutations, and KMT2A-PTD were identified in 10.0%, 0.8% and 1.9% of our patients respectively. Forty two percent of patients was restratified and 29.3% was up-staged from the IPSS-R. The IPSS-M had greater discriminative potential than IPSS-R and IPSS as indicated by higher Harrell’s concordance index. Patients with high, or very high-risk IPSS-M might benefit from allo-HSCT. Asides from the IPSS-M, age, ferritin level and 2022 ICC categorization predicted outcomes independently (Table 1). By analyzing demographic and genetic features from therapeutic standpoint, we suggested complementary genetic analyses including KMT2A-PTD for an accurate categorization by the IPSS-M for patients harboring ASXL1, TET2, STAG2, RUNX1, SF3B1, SRSF2, DNMT3A, U2AF1, and BCOR mutations or for patients who were classified as MDS, NOS with SLD/MLD based on 2022 ICC for patients. Summary/Conclusion: IPSS-M improved prognostic discrimination and optimized treatments for patients with 2022 ICC-defined MDS. Patients with high, or very high-risk IPSS-M might benefit from HSCT. In addition to 2022 ICC and other parameters, IPSS-M also provided independent prognostication. To facilitate the clinical implementation of the IPSS-M, we identify clinical and genetic characteristics for those patients who might receive different therapies if classified by the new score. Further multicenter prospective studies are warranted to confirm the utility of the IPSS-M model on different treatment modalities.Keywords: Myelodysplastic syndrome, Prognosis